We have identified three distinct human population groups which differ genetically in their risk for development of colorectal cancer and their pattern of development of disease. The three groups are: 1) patients with the autosomal dominant inherited disease, adenomantosis of the colon and rectum (familial polyposis); 2) patients who have inherited autosomal dominant colon cancer without polyposis; 3) patients in the general population with sporadic adenomas, and with primary colon cancer, both postulated to be inherited as a recessive genetic disorder, and which are known to be influenced by environmental factors. Carcinomas and adenomas (which are benigh but which have increased potential for malignant transformation) from these three population groups will be used in DNA transfection experiments with mouse 3T3 cells to determine: a) if the same or if different transforming genes are associated with colon cancer in each group: b) whether transforming gene activity can be detected in adenomas; c) and further whether the same or different transforming genes can be detected in benign tumors from the different groups. Previous work on the identification of human transforming genes has uitilized human tumor cell lines selected at random. This study represents the first approach towards characterization of human transforming genes in welldefined population groups, using fresh tissue taken at biopsy or surgery. Further, experiments we have carried out on 3T3 cells transformed with DNA from a human colon carcinoma cell line have identified changes in expression of specific peptides by twodimensional gel analysis. We will pursue this work in the cell lines to be established here to determine: a) whether all human transforming genes initialte the same changes in 35S-methionine or 32p-labeled peptides; b) whether the peptides are located in the cytoplasmic, membrane, or nuclear fraction; and c) whether the changes are present in the vitro translation products of mRNA from the transformed cells.